Abstract

Knowledge of the genetic architecture of pathogen infectivity and host resistance is essential for a mechanistic understanding of coevolutionary processes, yet the genetic basis of these interacting traits remains unknown for most host–pathogen systems. We used a comparative genomic approach to explore the genetic basis of infectivity in Pasteuria ramosa, a Gram-positive bacterial pathogen of planktonic crustaceans that has been established as a model for studies of Red Queen host–pathogen coevolution. We sequenced the genomes of a geographically, phenotypically, and genetically diverse collection of P. ramosa strains and performed a genome-wide association study to identify genetic correlates of infection phenotype. We found multiple polymorphisms within a single gene, Pcl7, that correlate perfectly with one common and widespread infection phenotype. We then confirmed this perfect association via Sanger sequencing in a large and diverse sample set of P. ramosa clones. Pcl7 codes for a collagen-like protein, a class of adhesion proteins known or suspected to be involved in the infection mechanisms of a number of important bacterial pathogens. Consistent with expectations under Red Queen coevolution, sequence variation of Pcl7 shows evidence of balancing selection, including extraordinarily high diversity and absence of geographic structure. Based on structural homology with a collagen-like protein of Bacillus anthracis, we propose a hypothesis for the structure of Pcl7 and the physical location of the phenotype-associated polymorphisms. Our results offer strong evidence for a gene governing infectivity and provide a molecular basis for further study of Red Queen dynamics in this model host–pathogen system.

中文翻译：

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全基因组关联分析确定了模型细菌病原体中传染性的遗传基础。

摘要

对病原菌感染性和宿主抗性的遗传结构的了解对于协同进化过程的机械理解至关重要，但是对于大多数宿主-病原体系统而言，这些相互作用性状的遗传基础仍然未知。我们使用比较基因组学方法探索了巴斯德巴斯德氏菌（一种浮游甲壳类革兰氏阳性细菌病原体）的传染性遗传基础，该细菌已被建立为研究红皇后宿主-病原体协同进化的模型。我们对P. ramosa菌株的地理，表型和遗传多样性收集的基因组进行了测序，并进行了全基因组关联研究，以确定感染表型的遗传相关性。我们在一个基因中发现了多个多态性，Pcl7与一种常见且广泛的感染表型完美相关。然后，我们通过对S. ram的测序，在大型和多样的P. ramosa克隆样本集中证实了这种完美关联。Pcl7编码胶原蛋白样蛋白，这是一类粘附蛋白，已知或怀疑与许多重要细菌病原体的感染机制有关。与Red Queen共同进化下的预期一致，Pcl7的序列变异显示出平衡选择的证据，包括异常高的多样性和缺乏地理结构。基于与炭疽芽孢杆菌胶原样蛋白的结构同源性，我们提出了Pcl7的结构和与表型相关的多态性的物理位置的假设。我们的结果为控制传染性的基因提供了有力的证据，并为进一步研究该模型宿主-病原体系统中的红皇后动力学提供了分子基础。